The Molecular Genetics and Hematopoiesis Program (Program 2) is an integrated and collaborative program with 23 members from 4 Departments. Program members are supported by $4,032,056 in peerreviewed funding (direct costs), with $1,744,246 from the NCI. Program members have a total of 308 peer-reviewed publications, including 22% intraprogrammatic and 12% interprogrammatic publications. The overall goals of the Program in Molecular Genetics and Hematopoiesis are: (1) to foster scientific interactions among investigators involved in clinical management and biological studies of hematological malignancies; (2) to promote translational research and facilitate the transfer of laboratory research to the management of patients with these diseases; and (3) to promote optimal use of resources within the University of Chicago Cancer Research Center and collaborating departments. Cytogenetic and molecular analysis of the hematological malignant diseases has led to the identification of many genes that are involved in normal hematopoiesis, as well as in the pathogenesis of leukemias and lymphomas. These insights have refined diagnostic and prognostic capabilities and have provided the foundation for risk-adapted, molecularly targeted therapeutics. Members of this program have had major roles in defining the pathogenetic events leading to hematological malignancies over the past 30 years. During the last five years, these important insights have begun to be translated into novel molecularly targeted approaches for the hematological malignancies. Program 2 is comprised of a tightly integrated group of investigators who are linked by common research themes and are working towards achievement of common goals. Specifically, the primary research goals of the investigators in Program 2 are: (1) to investigate mechanisms of normal and malignant hematopoiesis, and to elucidate pathogenetic pathways in hematologic cancers through the study of recurring chromosomal and molecular genetic aberrations in human leukemias and lymphomas; (2) to correlate recurring cytogenetic abnormalities and genetic mutations with the morphological, immunophenotypic, and clinical features of leukemia and lymphoma patients to define specific genetic risk groups based on better definition of molecular genetic pathways; (3) to develop, generate, and characterize animal model systems to dissect the functions of genes that are critical to both normal hematopoiesis and the development of hematopoietic diseases; and (4) to translate these insights into the design and conduct of novel risk-adapted clinical trials in hematological malignancies.